Project Summary/Abstract The overall goal of this research program is to understand how to regenerate mammalian central visual pathways. This proposal specifically focuses on the question of how to regenerate projections from output neurons of the eye, retinal ganglion cells (RGCs) to their targets in the brain (collectively referred to `retinofugal pathway')- a circuit absolutely essential vision. Significant progress has recently been made in identifying molecular programs capable of triggering some RGC axon regeneration. The next crucial milestones for the field are to discover ways to increase the number RGC axons that regenerate and the distance they regro. It is also crucially important to determine whether regenerating RGCs can find and reconnect to the correct targets, such visual capacities return. The three major aims of this proposal are to: 1) test the hypothesis that specific forms of visual stimulation can enhance the number and distance of RGC regenerating axons 2) test the hypothesis that combining visual stimulation with molecular triggers of RGC axon growth can cause RGC axons to regrow long distances back into the brain and 3) determine whether regenerating RGCs are capable of pathfinding back to and re-connecting to their appropriate targets, as well as avoiding targets incorrect for their function. Results from these experiments should lead to new understanding of how mammalian visual circuits can be replenished in response to injury and pave the way for the cultivation of tools applicable to humans suffering from vision loss.